Based on previous work by the principal investigator on the synthesis of inhibitors of the enzymatic activities of complement, the synthesis of additional candidate inhibitors is proposed. The specific objective is to synthesize analogs of m-(m-(p-nitrophenylureido) phenoxypropoxy)benzamidine, a potent inhibitor of whole complement hemolysis, and m-(o-(2-chloro-5- fluorosulfonylphenylureido)-phenoxy-butoxy)benzamidine, a potent irreversible inhibitor of the first component of complement. Established methods of synthesis will be employed. In addition, the available inhibitors as well as all new inhibitors will be examined for their spectrum of specificity by in vitro assay as inhibitors of trypsin, plasmin, and thrombin. An assay for Clr esterase activity will be developed. To do this, the proper substrate is needed. N-acetylglycyl-L- lysine-p-nitrophenyl ester and N-acetyl-L-arginine- p-nitrophenyl ester will be prepared as substrates for Clr. The effects of the compounds as inhibitors of whole complement hemolysis and of the first component of complement will be determined. Detailed studies of promising inhibitors will be carried out by Dr. David Bing at the Center for Blood Research, Boston, Massachusetts.